Many important cell functions depend on the surface presentation of molecules, so it is critical to determine the chemical state (composition, molecular structure, and orientation) and spatial distribution of biological moieties present in th near surface region of biomedical devices, as well as in the cells and tissues themselves. This requires development of surface analysis techniques capable of providing detailed surface chemical state information at high spatial resolutions both for 2-D imaging of surfaces and 3-D imaging of cells and tissues. A few years ago commercial cluster ion sources became available on time-of-flight secondary ion mass spectrometry (ToF-SIMS) instruments. These sources were capable of molecular depth profiling biological materials and opened the possibility of 3-D imaging with ToF-SIMS. This has resulted in a revolutionary change in the ToF-SIMS community and significantly increased interest of biomedical researchers in ToF-SIMS. The newly developed J105 Chemical Imager, a ToF-SIMS instrument with new capabilities, presents yet another significant advance in ToF-SIMS instrumentation for biomedical research. Its design represents several important advances over current commercial ToF-SIMS instruments: the decoupling of mass analysis from the primary ion beam sputtering process, a significantly larger depth of field for extraction of secondary ions, and the ability to do MS/MS experiments. In a traditional commercial ToF-SIMS instrument the spectral mass resolution is defined by the pulse width of the primary ion beam. In the J105 Chemical Imager, the mass analyzer defines the spectral mass resolution. This means direct current or long pulsed primary ion beams can be used, resulting in a 103 increase in count rates and the ability to acquire images with both high mass and spatial resolution. The large extraction depth of field means high-quality, SEM-like images can be obtained from rough and topologically complex samples such as stents and porous scaffolds. MS/MS experiments provide more detailed information about the composition and structure of ions. Now for the first time in a commercial ToF-SIMS instrument, the enhanced benefits of MS/MS analysis are available. An additional advantage of the J105 Chemical Imager is the MousetrapTM freeze fracture sample holder for analysis of hydrated biological materials. Research projects that will benefit from the new capabilities of the new J105 Chemical Imager ToF-SIMS instrument include analysis of medical implants (e.g., drug-loaded/coated stents), biofilms, cells, tissue sections, cell culture devices, tissue engineering scaffolds, microarray devices (DNA, antibody, carbohydrate, etc.), biosensors, etc.